Skip to main content
SpringerLink
Log in

The effects of GnRH antagonist on the endometrium of normally menstruating women

  • Pharmacology
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To study the effects of GnRH antagonist (ganirelix-Orgalutran®) on the endometrium of regularly menstruating women.

Materials and methods

Prospective, self-controlled study. The thirty-five volunteers were studied for two cycles: one as a control and the other, GnRH antagonist-treated cycles in which ganirelix 0.25 mg/d was given daily for 3 days, starting when the largest follicle reached 15 mm. In both cycles, serum estradiol, LH and endometrial thickness were measured when the largest follicle was ≥18 mm. Endometrial biopsy was performed on day 6 after ovulation for histological dating and morphometric study.

Results

No statistical differences between histological dating and the endometrial thickness in the control and GnRH antagonist-treated cycles. All morphometric parameters were also not different. Serum estradiol and LH levels were significantly lower in GnRH antagonist-treated cycles.

Conclusion

GnRH antagonist has no effect on the endometrium of regularly menstruating women as assessed by either histological dating or morphometric analysis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Daya S. Gonadotropin releasing hormone agonist protocols for pituitary desensitization in in vitro fertilization and gamete intrafallopian transfer cycles. Cochrane Database Syst Rev 2000;2:CD001299.

    PubMed  Google Scholar 

  2. Olivennes F, Cunha-Filho JS, Fanchin R, Bouchard P, Frydman R. The use of GnRH antagonists in ovarian stimulation. Hum Reprod Update 2002;8:279–90.

    Article  PubMed  CAS  Google Scholar 

  3. Newton C, Slota D, Yuzpe AA, Tummon IS. Memory complaints associated with the use of gonadotropin-releasing hormone agonists: a preliminary study. Fertil Steril 1996;65:1253–5.

    PubMed  CAS  Google Scholar 

  4. Warnock JK, Bundren JC, Morris DW. Depressive mood symptoms associated with ovarian suppression. Fertil Steril 2000;74:984–6.

    Article  PubMed  CAS  Google Scholar 

  5. Shapiro DB. Introduction. Fertil Steril 2003;80(suppl 1):S1–7.

    Article  PubMed  Google Scholar 

  6. The North American Ganirelix Study Group. Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation. Fertil Steril 2001;75:38–45.

    Article  Google Scholar 

  7. The European Orgalutran. Treatment with the gonadotropin-releasing hormone antagonist ganirelix in women undergoing ovarian stimulation with recombinant follicle stimulating hormone is effective, safe, and convenient: results of a controlled, randomized, multicentre trial. Hum Reprod 2000;15:1490–8.

    Article  Google Scholar 

  8. The European and Middle East Orgalutran. Comparable clinical outcome using the GnRH antagonist ganirelix or a long protocol of the GnRH agonist triptorelin for the prevention of premature LH surges in women undergoing ovarian stimulation. Hum Reprod 2001;16:644–51.

    Article  Google Scholar 

  9. Albano C, Felberbaum RE, Smitz J, Riethmüller-Winzen H, Engel J, Diedrich K, et al. Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)-antagonist cetrorelix and the LHRH-agonist buserelin. Hum Reprod 2000;15:526–31.

    Article  PubMed  CAS  Google Scholar 

  10. Olivennes F, Belaisch-Allart J, Emperaire JC, Dechuad H, Alvarez S, Moreau L, et al. Prospective, randomized, controlled study of in vitro fertilization-embryo transfer with a single dose of a luteinizing hormone-releasing hormone (LH-RH) antagonist (cetrorelix) or a depot formula of an LH-RH agonist (triptorelin). Fertil Steril 2000;73:314–20.

    Article  PubMed  CAS  Google Scholar 

  11. Al-Inany H, Aboulghar M. GnRH antagonist in assisted reproduction: a Cochrane review. Hum Reprod 2002;17:874–85.

    Article  PubMed  CAS  Google Scholar 

  12. Al-Inany H, Abou-Setta AM, Aboulghar M. Gonadotrophin-releasing hormone antagonists for assisted conception. Cochrane Database Syst Rev 2006;3:CD001750.

    PubMed  CAS  Google Scholar 

  13. Nikolettos N, Al-Hasani S, Felberbaum R, Demirel LC, Riethmüller-Winzen H, Reissmann T, et al. Comparison of cryopreservation outcome with human pronuclear stage oocytes obtained by the GnRH antagonist, Cetrorelix, and GnRH agonists. Eur J Obstet Gynaecol Reprod Biol 2000;93:91–5.

    Article  CAS  Google Scholar 

  14. Seelig AS, Al-Hasani S, Katalinic A, Schöpper B, Sturm R, Diedrich K, et al. Comparison of cryopreservation outcome with gonadotropin-releasing hormone agonists or antagonists in the collecting cycle. Fertil Steril 2002;77:472–5.

    Article  PubMed  Google Scholar 

  15. Kol S, Lightman A, Hillensjo T, Devroey P, Fauser B, Tarlatzis B, et al. High doses of gonadotrophin-releasing hormone antagonist in in-vitro fertilization cycles do not adversely affect the outcome of subsequent freeze–thaw cycles. Hum Reprod 1999;14:2242–4.

    Article  PubMed  CAS  Google Scholar 

  16. Hernandez ER. Embryo implantation and GnRH antagonists: Embryo implantation: the Rubicon for GnRH antagonists. Hum Reprod 2000;15:1211–6.

    Article  PubMed  CAS  Google Scholar 

  17. Dong KW, Marcelin K, Hsu MI, Chiang CM, Hoffman G, Roberts JL. Expression of gonadotropin-releasing hormone (GnRH) gene in human uterine endometrial tissue. Mol Hum Reprod 1998;4:893–8.

    Article  PubMed  CAS  Google Scholar 

  18. Raga F, Casan EM, Kruessel JS, Wen Y, Huang HY, Nezhat C, et al. Quantitative gonadotropin-releasing hormone gene expression and immunohistochemical localization in human endometrium throughout the menstrual cycle. Biol Reprod 1998;59:661–9.

    Article  PubMed  CAS  Google Scholar 

  19. Takeuchi S, Futamura N, Minoura H, Toyoda N. Possible direct effect of gonadotropin releasing hormone on human endometrium and decidua. Life Sci 1998;62:1187–94.

    Article  PubMed  CAS  Google Scholar 

  20. Acosta AA, Elberger L, Borghi M, Calamera JC, Chemes H, Doncel GF, et al. Endometrial dating and determination of the window of implantation in healthy fertile women. Fertil Steril 2000;73:788–98.

    Article  PubMed  CAS  Google Scholar 

  21. Li TC, Lenton EA, Rogers AW, Cooke ID, Dockery P. A new method of histologic dating of human endometrium in the luteal phase. Fertil Steril 1988;50:52–60.

    PubMed  CAS  Google Scholar 

  22. Bakos O, Lundkvist Ö, Wide L, Bergh T. Ultrasonographical and hormonal description of the normal ovulatory menstrual cycle. Acta Obstet Gynecol Scand 1994;73:790–6.

    Article  PubMed  CAS  Google Scholar 

  23. Ritchie WGM. Ultrasound in the evaluation of normal and induced ovulation. Fertil Steril 1985;43:167–81.

    PubMed  CAS  Google Scholar 

  24. Ecochard R, Boehringer H, Rabilloud M, Marret H. Chronological aspects of ultrasonic, hormonal, and other indirect indices of ovulation. Br J Obstet Gynaecol 2001;108:822–9.

    Article  CAS  Google Scholar 

  25. Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Fertil Steril 1950;1:3–25.

    Google Scholar 

  26. Johannisson E, Parker RA, Landgren BM, Diczfalusy E. Morphometric analysis of the human endometrium in relation to peripheral hormone levels. Fertil Steril 1982;38:564–71.

    PubMed  CAS  Google Scholar 

  27. Sereepapong W, Suwajanakorn S, Triratanachat S, Sampatanukul P, Pruksananonda K, Boonkasemsanti W, et al. Effects of clomiphene citrate on the endometrium of regularly cycling women. Fertil Steril 2000;73:287–91.

    Article  PubMed  CAS  Google Scholar 

  28. Fauser B, Devroey P. Why is the clinical acceptance of gonadotropin-releasing hormone antagonist cotreatment during ovarian hyperstimulation for in vitro fertilization so slow? Fertil Steril 2005;83:1607–11.

    Article  PubMed  Google Scholar 

  29. Griesinger G, Felderbaum R, Diedrich K. GnRH antagonists in ovarian stimulation: a treatment regimen of clinicians’ second choice? Data from the German national IVF registry. Hum Reprod 2005;20:2373–5.

    Article  PubMed  CAS  Google Scholar 

  30. The ganirelix dose-finding study group. A double-blind, randomized, dose-finding study to assess the efficacy of the gonadotropin-releasing hormone antagonist ganirelix (Org 37462) to prevent premature luteinizing hormone surges in women undergoing ovarian stimulation with recombinant follicle stimulating hormone (Puregon®). Hum Reprod 1998;13:3023–31.

    Article  Google Scholar 

  31. Kolibianakis E, Bourgain C, Albano C, Osmanagaoglu K, Smitz J, Van Steirteghem A, et al. Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin releasing hormone antagonists, and human chorionic gonadotropin on endometrial maturation on the day of oocyte pick-up. Fertil Steril 2002;78:1025–9.

    Article  PubMed  Google Scholar 

  32. Saadat P, Boostanfar R, Slater CC, Tourgeman DE, Stanczyk FZ, Paulson RJ. Accelerated endometrial maturation in the luteal phase of cycles utilizing controlled ovarian hyperstimulation: impact of gonadotropin-releasing hormone agonists versus antagonists. Fertil Steril 2004;82:167–71.

    Article  PubMed  CAS  Google Scholar 

  33. Griesinger G, Felberbaum RE, Schultze-Mosgau A, Diedrich K. Gonadotropin-releasing hormone antagonists for assisted reproductive techniques: are there clinical differences between agents? Drugs 2004;64:563–75.

    Article  PubMed  CAS  Google Scholar 

  34. Oberyé JJL, Mannaerts BMJL, Huisman JAM, Timmer CJ. Pharmacokinetic and pharmacodynamic characteristics of ganirelix (Antagon®/Orgalutran®). Part II. Dose-proportionality and gonadotropin suppression after multiples doses of ganirelix in healthy female volunteers. Fertil Steril 1999;72:1006–12.

    Article  PubMed  Google Scholar 

  35. Ueno J, Oehninger S, Brzyski RG, Acosta AA, Philput CB, Muasher SJ. Ultrasonographic appearance of the endometrium in natural and stimulated in-vitro fertilization cycles and its correlation with outcome. Hum Reprod 1991;6:901–4.

    PubMed  CAS  Google Scholar 

  36. Ohno Y, Hosokawa K, Tamura T, Fujimoto Y, Kawashima M, Koishi K, et al. Endometrial oestrogen and progesterone receptors and their relationship to sonographic appearance. Hum Reprod 1995;10:708–11.

    PubMed  CAS  Google Scholar 

  37. Ollendorff DA, Fejgin MD, Barzilai M, Ben-Noon I, Gerbie AB. The value of curettage in the diagnosis of ectopic pregnancy. Am J Obstet Gynecol 1987;157:71–2.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank Mettanando Bhikkhu for editing this manuscript. We are very grateful to Surasith Chaithongwongwatthana, M.D. for his useful advice on statistical analysis and Sarunya Numto, B.Sc. for her assistance in processing the endometrial specimens. This study would not have been possible without the generous cooperation of all volunteers who participated in this study. This study is supported by the Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University. Grant number: RA 178/47.

Author information

Authors and Affiliations

  1. Reproductive Medicine Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Rama IV Road, Bangkok, 10330, Thailand

    Porntip Sirayapiwat & Somchai Suwajanakorn

  2. Unit of Cyto-Pathology, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Rama IV Road, Bangkok, 10330, Thailand

    Surang Triratanachat & Somchai Niruthisard

Authors
  1. Porntip Sirayapiwat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Somchai Suwajanakorn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Surang Triratanachat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Somchai Niruthisard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Porntip Sirayapiwat.

Additional information

Capsule The endometrium of regularly menstruating volunteers on day 6 post ovulation after receiving GnRH antagonist were not different from the endometrium of natural cycle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sirayapiwat, P., Suwajanakorn, S., Triratanachat, S. et al. The effects of GnRH antagonist on the endometrium of normally menstruating women. J Assist Reprod Genet 24, 579–586 (2007). https://doi.org/10.1007/s10815-007-9184-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-007-9184-z

Keywords

Search

Navigation